Very interesting. When you talk about the relatively long half life. Do you mean the half of the glutathione increase following NAC? Or the half-life of nac itself?
I assume the former is the relevant one?
I guess my overarching question is: can we cycle nac+glycine and rapamycin, and if so how long a break in nac plus glycine prior to “rapamycin day”?
NAC itself. I don’t think glutathione is the factor here. NAC on its own is a free radical scavenger in the blood before it’s broken down. Its half life is approx 6 hours after an oral dose so not very long but long enough to counteract a lot of the effects of shorter mTOR inhibitors like glucosamine, astaxanthin and ashwagandha for example. Rapamycin of course lasts forever so less of an issue.
Glycine half life is super short so I wouldn’t worry about that at all. It’s not clear it has any nullifying effect either. Rapamycin lasts so long it’s hard not get some overlap with NAC unless you take NAC only like 1/2 days a week. If you choose shorter term mTOR inhibitors you can take stuff 3 times a day with not too much overlap of half-lives. I want to start astaxanthin but am worried it might do the same thing to glucosamine (which IMO is the molecule we have the most evidence for geroprotection in humans for) that NAC does. Going to try space out Ashwagandha, glucosamine, astaxanthin and NAC. Taurine, glycine, etc I don’t care too much when I take because they’re metabolised in minutes.
Upon further reading I’m less concerned about astaxanthin now. It’s an antioxidant but not an autophagy inhibitor. In fact it’s the opposite. NAC really is the only supplement I take that is an autophagy inhibitor. Need to time it well.
I believe you are right with your concern. Thanks for sharing. I agree that we need to be very careful with NAC. I wonder if we can say something about the doses? Would eg. 300 mg NAC a day be safe? But what a pity, as the other trials in favor of GlyNAC are so promising!
Interesting papers but… The dose makes the poison…:
So it’s might not be as bad as it sounds…
The latest study from May 2023 on the effects of GLYNAC on cognitive function.
The key findings of this study are that (1) compared to young mice, old mice have (a) cognitive impairment, (b) brain abnormalities with GSH deficiency, elevated OxS, impaired mitochondrial function, abnormal mitophagy and autophagy, diminished glucose transporters/uptake, elevated inflammation and higher genomic damage; (c) low brain neurotrophic factors (BDNF, GDNF and NGF); and (2) supplementing old mice with GlyNAC improved/reversed these brain defects, and improved cognition.
Glycine and NAC have a positive correlation to improved cognitive function. The Blue (Y) group is young mice. The Red (OC) and Green (OG) are old mice. OC is control. OG is old mice receiving GLYNAC. Pre is before receiving GLYNAC. Post is after. As you can see, GLYNAC reduced errors and helped mice navigate the maze almost as well as a young mouse!
The old-control mice had 69% (p < 0.001) lower total-GSH concentrations, and 75% (p < 0.05) lower reduced-GSH concentrations compared to young mice. Compared to old-control mice, the GlyNAC supplemented old mice had 156% higher total-GSH concentrations (p < 0.01) and 204% higher reduced-GSH concentrations (p < 0.001), and these results were not statistically different from values in young mice. There were no differences in oxidized glutathione concentrations (GSSG) between the three groups (Figure 3, Table 1).
I’m sceptical of all of this research coming out of Baylor. Pretty much all the positive longevity studies on glyNAC are from that team and guess what? They have a patent on glyNAC. Hoping the ITP tests it.
I’m aware that the ITP has tested glycine. It’s NAC I’m concerned about though. Lots of evidence it counteracts the mTOR inhibition benefits of rapa, glucosamine and Ashwagandha.
My father and I have been taking glycine and NAC for over a year. My father’s Glutathione levels are 945 which is amazing for his age. His levels are higher than most twenty somethings. Based on our blood work, it appears to work as promised. There is other literature available from other sources as well regarding the effects of glutathione.
There probably isn’t too much research into glycine and NAC due to both being inexpensive and readily available amino acids. But that doesn’t mean it doesn’t work.
Raising glutathione is one thing. It doing anything beneficial to people without any deficiency or morbidity is another. Further, it blocking the autophagic effects of rapamycin is again another question altogether.
I’d be happy to read any research outside of Baylor you can share as I have a lot of it and would love a reason to start taking it again.
You can reference Dr. Patel’s advice on Glutathione. He is not associated with Baylor but he’s another researcher in this space. His RCT on glutathione is in progress but was delayed by COVID. Taking Glycine and NAC is the best way to raise Glutathione (GSH), so this is all interrelated.
Key points:
Thanks, I’ll check it out. I do note he’s also got a patent on a topical cream however. History has made me very wary of anyone trying to sell anything in the longevity space.
I apologize for not following up with my experience. I have continued 100mg NACET daily for this entire time, along with 6g glycine, and a few other things I add and drop (12mg astraxanthin, 5000 IU vit D, 1mg finasteride, and 400mg Mg; 5g creatine now stopped due to taste and inconvenience but probably starting again). My “sore knees have gone away and caused likely that I started heavy lifting centered around deadlifts and not NAC. I occasionally get other soreness related to heavy deadlifts in different part of my legs (such as ligaments, muscles), but not being stupid and allowing time to recover and heal seems to work for me. So for me, I’m not sure NAC is an issue.
As part of this, I don’t look like a “muscle guy” ( cue @Agetron and @desertshores on the body building stage) and I’m not trying to become “big” (or “ripped” as the gen x-ers say, or “swol” as the Millennials say or “swol bruh’ as the gen z-ers say) — just “solid”, “athletic” and “healthy” looking (and actually healthy) — but in less than one year in December I reached my goal of squatting 2x my body weight (335 lbs in 2x 2 reps). It’s not Wolverine or Captain America levels, but for me that’s a huge improvement; there was a small crowd of people gathered around our small gym, mostly because there were a lot of plates for that gym and I really don’t look like a body builder, so that was pretty funny.
If you haven’t tried a boswellia serrata supplement you should give it a try.
Oddly, it has a special affinity for reducing knee pain.
Boswellia Serrata Extract offers several health benefits, including:
Reduction of Inflammation and Pain:
Contains boswellic acids with anti-inflammatory properties.
Reduces knee and joint pain.
Clinical studies indicate effectiveness in reducing pain and improving symptoms in osteoarthritis and rheumatoid arthritis patients.
Sadly it seems herbal supplements and I do not mix. I’ve developed allergies from most of them.
I’ve been taking 3g glycine in the morning, and sometimes a second 3g dose in the evening, but I think I’m going to cut it out for awhile.
Mainly because I think it’s making it really hard to build muscle. I’ve been stuffing myself all day every day and I can still barely gain weight. Right now I’m at around 188lbs, which at 6’3 is a good weight for health, but I’d like to be at around 210-220lbs for appearance and sports.
^ Saved that as a draft before I stopped glycine (and collagen) a couple months ago, and since then I’ve been able to put on about 8 lbs. This is despite picking up a mild kratom habit during that time (3-6g/daily), and starting to drink more on the weekends. I’ve also been way more active (aerobic stuff, but also just moving all day long) over the past couple months then I’ve been in a long time.
Anyways, all that is to say that if you’re trying to build muscle, maybe glycine is actively hurting. I guess I also cut back on rapamycin (only had a few doses over the past couple months), so maybe that has something to do with it, but I’m leaning towards glycine.
Definitely will hop back on glycine at some point, assuming I can maintain a desirable weight while on it. I was up to 203lbs last August, which was before I started rapa or glycine, and then got all the way down to 185lbs in February this year. Probably most of my weight loss was due to getting a busier schedule and not having time to stuff myself all day long, but maybe the rapa and glycine played a role also.
Is this perhaps due to glycine taking methionine out of circulation and driving it to glutathione? — methionine activates mTORC1 Through TAS1R1/TAS1R3. And glutathione is an antioxidant, so perhaps would separately dull the “muscle building signaling from damaged muscle”? So glycine would (somewhat) extend longevity but at the expense of muscle building.
(I heard this on a podcast, but in the sense of “take glycine to offset animal protein consumption for longevity”. Not sure if this is actually true, but seems to make some sense.
I take 6g of glycine and 30g of collagen, plus “adequate” animal protein (probably around 0.9g/lb-ish). So maybe this is why muscle building is slow regardless of how hard I kill it at the gym? And not that I’m a spritely) 53 yr old?
My guess would be that methionine depletion directly reduces protein synthesis, via reduced translation initiation. This is because in eukaryotes, methionine (technically speaking, charged methionine-tRNA) is required for translation initiation. Computational modeling also suggests that translation is generally rate-limited by translation initiation, rather than elongation. [ref]
Latest video on Glycine from Physionic.
I take glycine separate from melatonin. melatonin 10 at evening and it should be out of the system before I take about 12-15 grams of glycine with my coffee which should be out of the system by night
Novos doesn’t like nac, so I’m reticent on it. Hopefully glycine is enough to pump up glutathione.
I hope glycine doesn’t interact with rapa because it really gives me a boost throughout the day and has a lot of benefits to it health wise, a lot ive read. But it does the most for me in terms of energy/libido etc.
